Methanol → 6-methyl-pyrrolo[2,1-b]thiazole-7-carboxylic Acid Ethyl Ester

HRID 560327Notes

Reaction equation

HRID 560327 reaction equation
C[Zn]C.[CH2:4]([O:6][C:7]([C:9]1[C:10](Br)=[CH:11][N:12]2[CH:16]=[CH:15][S:14][C:13]=12)=[O:8])[CH3:5].CO.[CH3:20]C(OC)(C)C>C1(C)C=CC=CC=1.O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH2:4]([O:6][C:7]([C:9]1[C:10]([CH3:20])=[CH:11][N:12]2[CH:16]=[CH:15][S:14][C:13]=12)=[O:8])[CH3:5]

Participants

8

Reactant 4

HCID 887MethanolHCID 15413tert-Butyl methyl etherHCID 593168206-Bromo-pyrrolo[2,1-b]thiazole-7-carboxylic acid ethyl esterHCID 178477796HCID 178477796, compound

Product 1

HCID 593168376-methyl-pyrrolo[2,1-b]thiazole-7-carboxylic Acid Ethyl Ester

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent

Procedure

Under nitrogen atmosphere a solution of dimethylzinc in toluene (1.2 M, 19.1 mL) is added to a mixture of 6-bromo-pyrrolo[2,1-b]thiazole-7-carboxylic acid ethyl ester (11.4 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.23 mmol, complex with CH2Cl2) in dioxane (35 mL). The mixture is heated to reflux for 2 h, stirred at RT for 12 h and diluted by addition of MeOH (2.3 mL) and TBME. The mixture is washed with aq. HCl (1.0 M) and water, dried over MgSO4, concentrated in vacuo and purified by FC (gradient: heptane to heptane/EtOAc 8/2) to give the desired product. LC-MS: tR=0.91 min; [M+H]+=210.0.

Workup

  1. temperatureThe mixture is heated
  2. temperatureto reflux for 2 h
  3. washThe mixture is washed with aq. HCl (1.0 M) and water
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. custompurified by FC (gradient: heptane to heptane/EtOAc 8/2)

Sources & evidence

ORD record
ord-09496a5208b149d2b9366a87b5a6e492
Source dataset
uspto-grants-2011_11
Patent number
US08063099B2

Reaction notes

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